Large Study of ALL Patients Finds Lower Survival in Adolescent and Young Adult Patients

Eric Larsen, MD

A large phase III trial involving patients with high-risk acute lymphoblastic leukemia (HR-ALL) found that adolescent and young adult (AYA) patients between the ages of 16 and 30 had poorer outcomes when given the same treatment regimen as younger ALL patients.

Data from the study were released Friday at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago. Historically, AYA patients with ALL have poorer outcomes than patients younger than 16 years of age. Various studies have shown both higher rates of relapse and higher rates of toxicity in this AYA group of patients.

"This is a consistent finding in any observation you'll see in ALL," said Eric Larsen, MD, medical director of the Maine Children's Cancer Program and lead study author of the Children's Oncology group protocol AALL0232, the findings of which were the basis of this study.

Studies have suggested that factors such as disease biology, response to treatment, and compliance with treatment regimens all factor into differences in survival between young patients and AYA patients, but the study populations have been fairly small and had different definitions of the AYA range. Larsen said that while most studies have observed AYA up to age 18 or 21, this study chose an older group to assess whether those poorer outcomes remain consistent among patients aged 16 years and older.

Of the 2,571 eligible and evaluable patients enrolled in AALL0232, 501 were AYA patients under the age criteria set forth by the study. Patients were randomized to receive either dexamethasone or prednisone as a steroid during induction and high-dose methotrexate or scaling doses of methotrexate as maintenance therapy. Larsen explained that these stronger therapies might aid patients in controlling the disease, but they might also make the patients susceptible to greater levels of toxicity as a result.

The five-year event-free survival rate among AYA patients was 68.0% compared to 80.9% in the younger cohort, and five-year overall survival was 79.8% in the AYA group compared to 88.4% among younger patients (P <.0001 for both comparisons).

As expected, treatment failures were higher among AYA patients compared with younger patients. At five years of follow-up, 13.4% of patients younger than 16 relapsed, compared with 21.3% in the AYA group (P=.0018). The two primary forms of relapse observed were central nervous system (CNS) relapse and bone marrow relapse. In the AYA group, the CNS relapse rate over five years was 5.2% compared to 3.7% in the younger group (P=.58, not statistically significant), while the rate of bone marrow relapse was 15.2% compared to 9.0% in the younger group (P=.0007). The rate of post-induction remission deaths was 5.5% in AYA patients compared to 2.1 % in younger patients (P<.0001).

These results serve as a basis for determining how to design future treatment regimens for this difficult-to-treat population, Larsen said.

"Future strategies to improve outcomes in AYA patients with ALL should focus on both better leukemia control—that is, more intensification of therapy—and also attempts to reduce treatment toxicity," Larsen said.

Larsen E, Raetz EA, Winick NJ, et al. Outcome in adolescent and young adult (AYA) patients compared with younger patients treated for high-risk B-precursor acute lymphoblastic leukemia (HR-ALL): A report from the Children’s Oncology Group study AALL0232. J Clin Oncol. 2012;30(suppl: abstr CRA9508).

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